Danazol, a synthetic attenuated
anabolic steroid, has been administered for 36 months to a 32 year old male with hereditary
Protein S (PS) deficiency who had become non-compliant for
warfarin therapy. The patient has an eleven year history of
venous thrombosis. Since
danazol therapy was initiated, the patient has not experienced a thrombotic event or adverse side-effects. Levels of PS, other inhibitors, fibrinolytic components, and markers for
thrombin and platelet activation were measured prior and subsequent to
therapy. Following
danazol administration, marked and sustained increases were noted in Free
Protein S,
Antithrombin, and
Protein C. Platelet CD62 (
P-selectin) positivity which was elevated before
therapy, decreased to assay threshold limits within five weeks. Both
Prothrombin Fragment 1.2 and
thrombin-
antithrombin complexes were elevated post
danazol therapy indicating continued clearance of generated
thrombin. These data suggest that the protective effect provided by
danazol in this patient with hereditary PS deficiency, may in large part be due to suppression of platelet activation by
thrombin inhibition than simply through elevation of PS.